The Ia-2ß intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice.
Diabetologia
; 58(10): 2298-306, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26141787
ABSTRACT
AIMS/HYPOTHESIS:
miR-153 is an intronic miRNA embedded in the genes that encode IA-2 (also known as PTPRN) and IA-2ß (also known as PTPRN2). Islet antigen (IA)-2 and IA-2ß are major autoantigens in type 1 diabetes and are important transmembrane proteins in dense core and synaptic vesicles. miR-153 and its host genes are co-regulated in pancreas and brain. The present experiments were initiated to decipher the regulatory network between miR-153 and its host gene Ia-2ß (also known as Ptprn2).METHODS:
Insulin secretion was determined by ELISA. Identification of miRNA targets was assessed using luciferase assays and by quantitative real-time PCR and western blots in vitro and in vivo. Target protector was also employed to evaluate miRNA target function.RESULTS:
Functional studies revealed that miR-153 mimic suppresses both glucose- and potassium-induced insulin secretion (GSIS and PSIS, respectively), whereas miR-153 inhibitor enhances both GSIS and PSIS. A similar effect on dopamine secretion also was observed. Using miRNA target prediction software, we found that miR-153 is predicted to target the 3'UTR region of the calcium channel gene, Cacna1c. Further studies confirmed that Cacna1c mRNA and protein are downregulated by miR-153 mimics and upregulated by miR-153 inhibitors in insulin-secreting freshly isolated mouse islets, in the insulin-secreting mouse cell line MIN6 and in the dopamine-secreting cell line PC12. CONCLUSIONS/INTERPRETATION:
miR-153 is a negative regulator of both insulin and dopamine secretion through its effect on Cacna1c expression, which suggests that IA-2ß and miR-153 have opposite functional effects on the secretory pathway.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Dopamina
/
Canales de Calcio Tipo L
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MicroARNs
/
Insulina
Límite:
Animals
Idioma:
En
Revista:
Diabetologia
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos